Page 12 - nutrition

Maturitas 143 (2021) 1–9
H. Shakoor et al.
Table 1 (continued) related to incidence of COVID-19, nor did it explain differences in de-
mographic variation of infection rates [19,20]. It appears that associa-
Reference Design/study Risk of Bias Finding
type tions with vitamin D and COVID-19 rely heavily on univariate analysis
and do not remain consistent after adjustment for important con-
magnesium in
COVID-19 founding variables, such as comorbidity and sociodemographic factors.
Iotti et al. Perspective n/a Suggests a role for While it is unclear whether vitamin D status affects infection rates, there
[51] magnesium in is evidence to suggest a role in mitigating disease severity. The mortality
COVID-19 rates related to COVID-19 vary from country to country, and in the
Vitamin A
De Andrade Review n/a Suggests a role for southern hemisphere the mortality rates are lower than in the northern
et al. [52] vitamin A deficiency hemisphere [21]. One hypothesis explaining this pattern is that people
in COVID-19 in the northern hemisphere classically have more prevalent vitamin D
deficiency, due to lack of sun exposure in winter as compared to summer
period in the southern hemisphere during peak pandemic months
IL-2 and interferon-gamma (INF-γ). Vitamin D also promotes (January-May) [21]. It has also been shown that countries with higher
anti-inflammatory cytokines by Th2 cells and indirectly suppressing Th1
prevalence of vitamin D deficiency tend to have a higher burden of
cells diverting pro-inflammatory cells to an anti-inflammatory pheno-
COVID-19 morbidity and mortality [22]. Spain and Italy have high
type as well as stimulating suppressive regulatory T cells [15].
prevalence of vitamin D deficiency, which is linked with other important
Deficiency in vitamin D has been suggested to increase incidence and
health factors including, hypertension, diabetes, obesity and ethnicity,
severity of COVID-19 infection. COVID-19 patients have been repeatedly which appear to be associated with an increased risk of severe COVID-19
shown to have lower levels of vitamin D, with mean plasma concen-
infection. Evidence has shown directly that mortality rate is higher in
trations half that of controls [16], though the selection of the study COVID-19 patients with vitamin D deficiency and the mortality rate is
cohort was unclear, and unadjusted relative to important confounders,
lower in Nordic countries (Norway, Sweden, Iceland, Finland,
leaving their conclusions unclear. Therefore, supplementation of Greenland and Denmark) [21] possibly because of the rarity of vitamin
vitamin D is suggested to boost immunity against COVID-19 and reduce
D deficiency due to widespread supplement use. In addition, C-reactive
human mortality; however this hypothesis needs to be tested in human protein (CRP), a marker of inflammation and surrogate marker for
trials. It has also been suggested that adequate vitamin D levels may help
cytokine storm, was highly expressed in patients with severe COVID-19
to protect the respiratory epithelium from pathogenic invasion, symptoms and correlated with vitamin D deficiency [23]. Likewise, a
decreasing risk of infection. A pre-print population study in Israel also
pre-print retrospective study of twenty COVID-19 patients, showed a
found that vitamin D correlated with disease incidence, even after
link between vitamin D insufficiency and severe COVID-19. The par-
adjustment for sociodemographic and comorbidity variables [17]. This
ticipants with vitamin D inefficiency were more likely to have coagul-
finding is also supported in an additional pre-print study, currently
opathy and suppressed immune function [24]. in another study patients
under review [18], however these results must be corroborated. How- with deficiency were more likely to require intensive care admission in
ever, large biobank studies concluded that vitamin D deficiency was not
134 inpatients [25] While mechanistic understanding of the role of

Fig. 2. Immunomodulatory actions of vitamin D.IL: interleukin; TNF: Tumor necrosis factor; IFN: Interferon; Th: T-Helper; 7-DHC: 7-Dehydrocholesterol; PGE2:
Prostaglandin E2.

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